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1.
Pharmaceuticals ; 15(4):445, 2022.
Article in English | MDPI | ID: covidwho-1776312

ABSTRACT

Over the past two years, several variants of SARS-CoV-2 have emerged and spread all over the world. However, infectivity, clinical severity, re-infection, virulence, transmissibility, vaccine responses and escape, and epidemiological aspects have differed between SARS-CoV-2 variants. Currently, very few treatments are recommended against SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. Ivermectin is an antihelminthic agent that previously showed in vitro effects against a SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and omicron). The in vitro activity of ivermectin was compared to those of chloroquine and remdesivir. Unlike chloroquine (EC50 from 4.3 ±2.5 to 29.3 ±5.2 µM) or remdesivir (EC50 from 0.4 ±0.3 to 25.2 ±9.4 µM), ivermectin showed a relatively homogeneous in vitro activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ±0.5 to 6.7 ±0.4 µM), except for one omicron strain (EC50 = 1.3 ±0.5 µM). Ivermectin (No. EC50 = 219, mean EC50 = 5.7 ±1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = 214, mean EC50 = 16.1 ±9.0 µM) (p = 1.3 ×10−34) and remdesivir (No. EC50 = 201, mean EC50 = 11.9 ±10.0 µM) (p = 1.6 ×10−13). These results should be interpreted with caution regarding the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients.

2.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-330761

ABSTRACT

Genetic recombination is a major evolutionary mechanism among RNA viruses, and it is common in coronaviruses, including those infecting humans. A few SARS-CoV-2 recombinants have been reported to date whose genome harbored combinations of mutations from different mutants or variants, but a single patient sample was analyzed, and the virus was not isolated. Here, we report the gradual creation of a hybrid genome of B.1.160 and Alpha variants in a lymphoma patient chronically infected for 14 months, and we isolated the recombinant virus. The hybrid genome was obtained by next-generation sequencing, and recombination sites were confirmed by PCR. This consisted of a parental B.1.160 backbone interspersed with two fragments, including the spike gene, from an Alpha variant. Analysis of seven sequential samples from the patient decoded the recombination steps, including the initial infection with a B.1.160 variant, then a concurrent infection with this variant and an Alpha variant, the generation of hybrid genomes, and eventually the emergence of a predominant recombinant virus isolated at the end of the patient follow-up. This case exemplifies the recombination process of SARS-CoV-2 in real life, and it calls for intensifying genomic surveillance in patients coinfected with different SARS-CoV-2 variants, and more generally with several RNA viruses, as this may lead to the creation of new viruses.

3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329745

ABSTRACT

Multiple SARS-CoV-2 variants have successively, or concommitantly spread worldwide since summer 2020. A few co-infections with different variants were reported and genetic recombinations, common among coronaviruses, were reported or suspected based on co-detection of signature mutations of different variants in a given genome. Here were report three infections in southern France with a Delta 21J/AY.4-Omicron 21K/BA.1 “Deltamicron” recombinant. The hybrid genome harbors signature mutations of the two lineages, supported by a mean sequencing depth of 1,163-1,421 reads and mean nucleotide diversity of 0.1-0.6%. It is composed of the near full-length spike gene (from codons 156-179) of an Omicron 21K/BA.1 variant in a Delta 21J/AY.4 lineage backbone. It is similar to those reported for 15 other patients sampled since January 2022 in Europe. Importantly, we cultured an isolate of this recombinant and sequenced its genome. It was observed by scanning electron microscopy. As it is misidentified with current variant screening qPCR, we designed and implemented for routine diagnosis a specific duplex qPCR. Finally, structural analysis of the recombinant spike suggested its hybrid content could optimize viral binding to the host cell membrane. These findings prompt further studies of the virological, epidemiological, and clinical features of this recombinant.

4.
J Med Virol ; 2022 Mar 03.
Article in English | MEDLINE | ID: covidwho-1729155

ABSTRACT

The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here, we describe the first cases diagnosed with this variant in south-eastern France. We identified 13 cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travelers returning from Tanzania. Overall, viral genomes displayed a mean (±standard deviation) number of 65.9 ± 2.5 (range, 61-69) nucleotide substitutions and 31.0 ± 8.3 (27-50) nucleotide deletions, resulting in 49.6 ± 2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4 ± 1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions highlighted a significant enlargement and flattening of the surface of the 21L/BA.2 N-terminal domain of the spike protein compared to that of the 21K/BA.1 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country, and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.

5.
Frontiers in microbiology ; 12, 2021.
Article in English | EuropePMC | ID: covidwho-1696164

ABSTRACT

After the end of the first epidemic episode of SARS-CoV-2 infections, as cases began to rise again during the summer of 2020, we at IHU Méditerranée Infection in Marseille, France, intensified the genomic surveillance of SARS-CoV-2, and described the first viral variants. In this study, we compared the incidence curves of SARS-CoV-2-associated deaths in different countries and reported the classification of SARS-CoV-2 variants detected in our institute, as well as the kinetics and sources of the infections. We used mortality collected from a COVID-19 data repository for 221 countries. Viral variants were defined based on ≥5 hallmark mutations along the whole genome shared by ≥30 genomes. SARS-CoV-2 genotype was determined for 24,181 patients using next-generation genome and gene sequencing (in 47 and 11% of cases, respectively) or variant-specific qPCR (in 42% of cases). Sixteen variants were identified by analyzing viral genomes from 9,788 SARS-CoV-2-diagnosed patients. Our data show that since the first SARS-CoV-2 epidemic episode in Marseille, importation through travel from abroad was documented for seven of the new variants. In addition, for the B.1.160 variant of Pangolin classification (a.k.a. Marseille-4), we suspect transmission from farm minks. In conclusion, we observed that the successive epidemic peaks of SARS-CoV-2 infections are not linked to rebounds of viral genotypes that are already present but to newly introduced variants. We thus suggest that border control is the best mean of combating this type of introduction, and that intensive control of mink farms is also necessary to prevent the emergence of new variants generated in this animal reservoir.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314917

ABSTRACT

Background: From mid-March to mid-April 2020, the French aircraft carrier Charles de Gaulle suffered a COVID-19 outbreak. An investigation was performed to describe the outbreak, including how the virus was introduced on board. We present the clinical pictures of COVID-19 cases with risk factors for infection and severity, effectiveness of preventive measures, and we discuss the real collective protective rate.Methods: A confirmed case was any service member with a positive SARS-CoV-2 RT-PCR and/or who presented symptoms of anosmia and/or ageusia. We considered the entire crew as a cohort and questioned them about individual, epidemiological, and clinical data. We performed viral genome sequencing and searched for SARS-CoV-2 in the environment.Results: The attack rate was 65% (1085/1767). The sex ratio was 6·9, and median age was 29 years. There were four clinical profiles: asymptomatic (13·0%), non-specific symptomatic (8·1%), specific symptomatic (76·3%), and severe (i.e. requiring oxygen therapy, 2·6%). Active smoking prevented severe COVID-19;age and obesity were risk factors.The instantaneous reproduction rate Rt and viral sequencing supported the hypothesis of several introductions of the virus on board, with an acceleration of the Rt when preventive measures were lifted. Physical distancing prevented infection (ORa, 0·55, 95% CI, 0·40-0·76). In the end, transmission stopped when the proportion of infected personnel was large enough to prevent the virus from circulating (65%, 95% CI, 62-68).Discussion: Asymptomatic and non-specific clinical pictures of COVID-19, combined with a lack of knowledge at that time about the specific symptoms of COVID-19 (anosmia, ageusia), delayed detection of the outbreak. Once it was identified, the lack of an isolation ward made it difficult to manage transmission on board, and the outbreak spread until a collective protective rate was reached. However, physical distancing was effective when applied. Syndromic surveillance and point-of-care biology could enable early detection of such viral emergences or outbreaks.Funding Information: No funding to declare.Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This was not an experimental protocol, but an outbreak investigation with routine care provided to infected individuals, so no ethical approval from any named institutional and/or licensing/ethics committee was required. We obtained individual informed consent to analyze data. No administrative authorization was required to access and use medical records. We chose not to provide certain details and to aggregate certain data in order to maintain patient anonymity. All methods were carried out in accordance with relevant guidelines and regulations.

7.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327546

ABSTRACT

ABSTRACT The SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here we describe the first cases diagnosed with this variant in south-eastern France. We identified thirteen cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travellers returning from Tanzania. Overall, viral genomes displayed a mean (±standard deviation) number of 65.9±2.5 (range, 61-69) nucleotide substitutions and 31.0±8.3 (27-50) nucleotide deletions, resulting in 49.6±2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4±1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions pointed out a significant enlargement and flattening of the 21L/BA.2 N-terminal domain surface compared with that of the 21K/BA.2 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.

8.
Travel Med Infect Dis ; 46: 102277, 2022.
Article in English | MEDLINE | ID: covidwho-1677190

ABSTRACT

BACKGROUND: We describe the epidemiology of the first cases diagnosed in our institute of infections with the SARS-CoV-2 Beta variant and how this variant was imported to Marseille. METHODS: The Beta variant was identified based on analyses of sequences of viral genomes or of a spike gene fragment obtained by next-generation sequencing using Illumina technology, or by a real-time reverse-transcription-PCR (qPCR) specific of the Beta variant. RESULTS: The first patient diagnosed as infected with the SARS-CoV-2 Beta variant was sampled on January 15, 2021. Twenty-nine patients were diagnosed in January 2021 (two weeks). Fifteen (52%) patients were of Comorian nationality. Eight (28%) had travelled abroad, including six who had returned from Comoros. Phylogeny based on SARS-CoV-2 genomes from 11 of these patients and their best BLAST hits from the GISAID database showed that seven patients, including the four returning from Comoros, were clustered with 27 other genomes from GISAID that included the six first Beta variant genomes described in Comoros in January 2021. CONCLUSIONS: Our analyses highlight that, as for the case of other SARS-CoV-2 variants that have been diagnosed in Marseille, the Beta variant was imported to Marseille through travel from abroad. It had limited spread in our geographical area.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Comoros/epidemiology , Genome, Viral , Humans , Mutation , Phylogeny , SARS-CoV-2/genetics
9.
Arch Virol ; 167(2): 583-589, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1653517

ABSTRACT

We detected SARS-CoV-2 of PANGO lineage R.1 with the spike substitution E484K in three patients. Eleven other sequences in France and 8,831 worldwide were available from GISAID, 92% originating from Japan. The three genome sequences from our institute were phylogenetically closest to another from Guinea-Conakry, where one of the patients had travelled. These viruses did not exhibit any unusual features in cell culture. Spike structural predictions indicated a 1.3-time higher transmissibility index than for the globally spread B.1.1.7 variant but also an affinity loss for gangliosides that might have slowed dissemination. The spread of new SARS-CoV-2 mutants/variants is still not well understood and therefore difficult to predict, and this hinders implementation of effective preventive measures, including adapted vaccines.


Subject(s)
COVID-19 , SARS-CoV-2 , Guinea , Humans , Mutation , Spike Glycoprotein, Coronavirus/genetics
10.
Travel Med Infect Dis ; 45: 102236, 2022.
Article in English | MEDLINE | ID: covidwho-1641695

ABSTRACT

BACKGROUND: The purpose of the study was to challenge the hypothesis of an introduction of influenza viruses by international travellers and subsequent local circulation in Marseille, France. METHODS: We analysed the epidemiological data of PCR-confirmed cases over an eight-year period and compared the genomic data of local and imported influenza viruses during a six-month period. RESULTS: Between June 2013 and December 2020, 12,434 patients in the Assistance Publique-Hospitaux de Marseille were diagnosed with an influenza virus infection at the laboratory of the Institut Hospitalo-Universitaire Méditerranéee Infection of Marseille. Half of the patients were below the age of 20. Most of the imported cases were diagnosed outside of epidemic periods. Fourteen genomes of the influenza A virus, including six in international travellers returning from Europe or from the Arabian Peninsula and eight from patients who had not travelled were analysed. Sequences of influenza A/H1N1 virus genomes detected in subjects who had travelled to Saudi Arabia were in the same clade and differed from sequences detected later in a traveller returning from Italy, and in non-travellers who were infected in Marseille. This suggests that influenza viruses imported from Saudi Arabia did not subsequently circulate in Marseille. CONCLUSION: Future studies with higher numbers of genomes are needed to confirm this result.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza, Human , France/epidemiology , Genomics , Humans , Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/diagnosis , Influenza, Human/epidemiology , Travel
11.
Front Biosci (Landmark Ed) ; 26(12): 1493-1502, 2021 12 30.
Article in English | MEDLINE | ID: covidwho-1614662

ABSTRACT

BACKGROUND: Despite the fact that the clinical efficacy of hydroxychloroquine is still controversial, it has been demonstrated in vitro to control SARS-CoV-2 multiplication on Vero E6 cells. In this study, we tested the possibility that some patients with prolonged virus excretion could be infected by less susceptible strains. METHOD: Using a high-content screening method, we screened 30 different selected isolates of SARS-CoV-2 from different patients who received azithromycin ± hydroxychloroquine. We focused on patients with viral persistence, i.e., positive virus detection in a nasopharyngeal sample ≥10 days, and who were tested during two French epidemic waves, late winter-spring of 2020 and the summer of 2020. Dose-response curves in single-molecule assays with hydroxychloroquine were created for isolates with suspected reduced susceptibility. Genome clustering was performed for all isolates. RESULTS: Of 30 tested strains, three were detected as replicating in the presence of azithromycin + hydroxychloroquine, each at 5 µM. The dose-response model showed a decrease in susceptibility of these three strains to hydroxychloroquine. Whole genome sequencing revealed that these three strains are all from the second epidemic wave and two cluster with isolates from Africa. CONCLUSIONS: Reduced susceptibility to hydroxychloroquine was not associated with viral persistence in naso-pharyngeal samples. Rather, it was associated with occurring during the second epidemic wave, which began in the summer and with strains clustering with those with a common genotype in Africa, where hydroxychloroquine was the most widely used.


Subject(s)
COVID-19 , Hydroxychloroquine , Azithromycin/pharmacology , COVID-19/drug therapy , Humans , Hydroxychloroquine/pharmacology , SARS-CoV-2
12.
Virus Genes ; 58(1): 53-58, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1536341

ABSTRACT

Great concerns have been raised about SARS-CoV-2 variants over the past six months. At the end of 2020, an increasing incidence of spike substitutions Q677H/P was described in the USA, which involved six independent lineages. We searched for changes to this amino acid in the sequence database of SARS-CoV-2 genomes obtained at the IHU Méditerranée Infection (Marseille, France) from 3634 patients sampled between February 2020 and April 2021. In seven genomes (0.2%), we found a deletion of five amino acids at spike positions 675-679 (QTQTN) including Q677, and in 76 genomes (2.3%) we found a Q677H substitution. The 83 genomes were classified in ten different Pangolin lineages. Genomes with a spike Q677 deletion were obtained from respiratory samples collected in six cases between 28 March 2020 and 12 October 2020 and in one case on 1 February 2021. The Q677H substitution was found in genomes all obtained from respiratory samples collected from 19 January 2021 and were classified in seven different lineages. Most of these genomes (41 cases) were of UK variant. Two others were classified in the B.1.160 Pangolin lineage (Marseille-4 variant) which was first detected in July 2020 in our institute but was devoid of this substitution until 19 January 2021. Also, eight genomes were classified in the A.27/Marseille-501 lineage which was first detected in our institute in January 2021 and which either harboured or did not harbour the Q677H substitution. Thus, the spike Q677H substitution should be considered as another example of convergent evolution, as it is the case of spike substitutions L18F, E484K, L452R, and N501Y which also independently appeared in various lineages.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Amino Acid Substitution , Amino Acids , COVID-19/virology , France , Humans , Mutation , Phylogeny , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
13.
Travel Med Infect Dis ; 44: 102183, 2021.
Article in English | MEDLINE | ID: covidwho-1473503

ABSTRACT

BACKGROUND: Several outbreaks of pneumococcal pneumonia among shipyard workers have been described. In this study, following a previous report of grouped cases, we aimed to elucidate the features of disease onset. METHODS: We compared the population characteristics of shipyard workers with a confirmed diagnosis of pneumococcal pneumonia (N = 38) to those of workers without pneumonia (N = 53). We compared nine S. pneumoniae strains isolated from patients with pneumonia by capsular serotyping, multi-locus sequence typing, and whole genome sequencing. RESULTS: Shipyard workers with Streptococcus pneumoniae pneumonia were more frequently from Italy (P = 0.016), had at least one underlying condition (P = 0.024), lived on-board the ship (P = 0.009). None of these factors was independent by multivariate analysis. While capsular serotyping enabled us to identify four different serotypes: 4 (n = 5), 8 (n = 2), 9 N (n = 1), and 3 (n = 1), by sequence typing, we distinguished five sequence types (STs): ST801 (n = 4), ST205 (n = 2), ST1220 (n = 1), ST1280 (n = 1), and ST66 (n = 1). Whole genome sequencing confirmed the results obtained by MLST. Genomes of isolates of the same sequence type were similar with ≤80 single-nucleotide polymorphisms. CONCLUSIONS: We confirmed that the onset of pneumococcal infection among shipyard workers was attributable to both a person-to-person spread of single strains of S. pneumoniae and a shift of different strains from commensal to pathogen under favourable conditions (professional exposure, viral infections). Control measures should therefore be implemented by taking into account these features.


Subject(s)
Pneumococcal Infections , Pneumonia, Pneumococcal , Humans , Multilocus Sequence Typing , Pneumonia, Pneumococcal/epidemiology , Serogroup , Serotyping , Streptococcus pneumoniae/genetics
14.
Transbound Emerg Dis ; 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1488270

ABSTRACT

Since the start of the coronavirus disease of 2019 (COVID-19) pandemic, several episodes of human-to-animal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission have been described in different countries. The role of pets, especially domestic dogs, in the COVID-19 epidemiology is highly questionable and needs further investigation. In this study, we report a case of COVID-19 in a French dog living in close contact with its owners who were COVID-19 patients. The dog presented rhinitis and was sampled 1 week after its owners (a man and a woman) were tested positive for COVID-19. The nasal swabs for the dog tested remained positive for SARS-CoV-2 by reverse transcription quantitative real-time PCR (RT-qPCR) 1 month following the first diagnosis. Specific anti-SARS-CoV-2 antibodies were detectable 12 days after the first diagnosis and persisted for at least 5 months as tested using enzyme-linked immunoassay (ELISA) and automated western blotting. The whole-genome sequences from the dog and its owners were 99%-100% identical (with the man and the woman's sequences, respectively) and matched the B.1.160 variant of concern (Marseille-4 variant), the most widespread in France at the time the dog was infected. This study documents the first detection of B.1.160 in pets (a dog) in France, and the first canine genome recovery of the B.1.160 variant of global concern. Moreover, given the enhanced infectivity and transmissibility of the Marseille-4 variant for humans, this case also highlights the risk that pets may potentially play a significant role in SARS-CoV-2 outbreaks and may transmit the infection to humans. We have evidence of human-to-dog transmission of the Marseille-4 variant since the owners were first to be infected. Finally, owners and veterinarians must be vigilent for canine COVID-19 when dogs are presented with respiratory clinical signs.

15.
Front Microbiol ; 12: 675528, 2021.
Article in English | MEDLINE | ID: covidwho-1456295

ABSTRACT

The rapid spread of SARS-CoV-2 variants has quickly spanned doubts and the fear about their ability escape vaccine protection. Some of these variants initially identified in caged were also found in humans. The claim that these variants exhibited lower susceptibility to antibody neutralization led to the slaughter of 17 million minks in Denmark. SARS-CoV-2 prevalence tests led to the discovery of infected farmed minks worldwide. In this study, we revisit the issue of the circulation of SARS-CoV-2 variants in minks as a model of sarbecovirus interspecies evolution by: (1) comparing human and mink angiotensin I converting enzyme 2 (ACE2) and neuropilin 1 (NRP-1) receptors; (2) comparing SARS-CoV-2 sequences from humans and minks; (3) analyzing the impact of mutations on the 3D structure of the spike protein; and (4) predicting linear epitope targets for immune response. Mink-selected SARS-CoV-2 variants carrying the Y453F/D614G mutations display an increased affinity for human ACE2 and can escape neutralization by one monoclonal antibody. However, they are unlikely to lose most of the major epitopes predicted to be targets for neutralizing antibodies. We discuss the consequences of these results for the rational use of SARS-CoV-2 vaccines.

16.
Infect Genet Evol ; 95: 105092, 2021 11.
Article in English | MEDLINE | ID: covidwho-1433676

ABSTRACT

OBJECTIVES: To compare the demographics, clinical characteristics and severity of patients infected with nine different SARS-CoV-2 variants, during three phases of the COVID-19 epidemic in Marseille. METHODS: A single centre retrospective cohort study was conducted in 1760 patients infected with SARS-CoV-2 of Nextstrain clades 20A, 20B, and 20C (first phase, February-May 2020), Pangolin lineages B.1.177 (we named Marseille-2) and B.1.160 (Marseille-4) variants (second phase, June-December 2020), and B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and A.27 (Marseille-501) variants (third phase, January 2021-today). Outcomes were the occurrence of clinical failures, including hospitalisation, transfer to the intensive-care unit, and death. RESULTS: During each phase, no major differences were observed with regards to age and gender distribution, the prevalence of chronic diseases, and clinical symptoms between variants circulating in a given phase. The B.1.177 and B.1.160 variants were associated with more severe outcomes. Infections occurring during the second phase were associated with a higher rate of death as compared to infections during the first and third phases. Patients in the second phase were more likely to be hospitalised than those in the third phase. Patients infected during the third phase were more frequently obese than others. CONCLUSION: A large cohort study is recommended to evaluate the transmissibility and to better characterise the clinical severity of emerging variants.


Subject(s)
COVID-19/pathology , Diabetes Mellitus/pathology , Genome, Viral , Hypertension/pathology , Obesity/pathology , SARS-CoV-2/pathogenicity , Adult , Aged , COVID-19/epidemiology , COVID-19/mortality , COVID-19/virology , Comorbidity , Diabetes Mellitus/epidemiology , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Female , France/epidemiology , Genotype , Heart Diseases/epidemiology , Heart Diseases/mortality , Heart Diseases/pathology , Heart Diseases/virology , Hospitalization/statistics & numerical data , Hospitals , Humans , Hypertension/epidemiology , Hypertension/mortality , Hypertension/virology , Intensive Care Units , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/mortality , Neoplasms/pathology , Neoplasms/virology , Obesity/epidemiology , Obesity/mortality , Obesity/virology , Phylogeny , Retrospective Studies , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sequence Analysis, RNA , Severity of Illness Index , Survival Analysis
17.
Front Med (Lausanne) ; 8: 737602, 2021.
Article in English | MEDLINE | ID: covidwho-1430710

ABSTRACT

Since the start of COVID-19 pandemic the Republic of Djibouti, in the horn of Africa, has experienced two epidemic waves of the virus between April and August 2020 and between February and May 2021. By May 2021, COVID-19 had affected 1.18% of the Djiboutian population and caused 152 deaths. Djibouti hosts several foreign military bases which makes it a potential hot-spot for the introduction of different SARS-CoV-2 strains. We genotyped fifty three viruses that have spread during the two epidemic waves. Next, using spike sequencing of twenty-eight strains and whole genome sequencing of thirteen strains, we found that Nexstrain clades 20A and 20B with a typically European D614G substitution in the spike and a frequent P2633L substitution in nsp16 were the dominant viruses during the first epidemic wave, while the clade 20H South African variants spread during the second wave characterized by an increase in the number of severe forms of COVID-19.

18.
Nature ; 595(7869): 713-717, 2021 07.
Article in English | MEDLINE | ID: covidwho-1287812

ABSTRACT

After the first wave of SARS-CoV-2 infections in spring 2020, Europe experienced a resurgence of the virus starting in late summer 2020 that was deadlier and more difficult to contain1. Relaxed intervention measures and summer travel have been implicated as drivers of the second wave2. Here we build a phylogeographical model to evaluate how newly introduced lineages, as opposed to the rekindling of persistent lineages, contributed to the resurgence of COVID-19 in Europe. We inform this model using genomic, mobility and epidemiological data from 10 European countries and estimate that in many countries more than half of the lineages circulating in late summer resulted from new introductions since 15 June 2020. The success in onward transmission of newly introduced lineages was negatively associated with the local incidence of COVID-19 during this period. The pervasive spread of variants in summer 2020 highlights the threat of viral dissemination when restrictions are lifted, and this needs to be carefully considered in strategies to control the current spread of variants that are more transmissible and/or evade immunity. Our findings indicate that more effective and coordinated measures are required to contain the spread through cross-border travel even as vaccination is reducing disease burden.


Subject(s)
COVID-19/transmission , COVID-19/virology , SARS-CoV-2/isolation & purification , COVID-19/epidemiology , COVID-19/prevention & control , Europe/epidemiology , Genome, Viral/genetics , Humans , Incidence , Locomotion , Phylogeny , Phylogeography , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Time Factors , Travel/statistics & numerical data
19.
J Clin Med ; 10(12)2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1270066

ABSTRACT

BACKGROUND: We conducted this review to summarize the relation between viral mutation and infectivity of SARS-CoV-2 and also the severity of COVID-19 in vivo and in vitro. METHOD: Articles were identified through a literature search until 31 May 2021, in PubMed, Web of Science and Google Scholar. RESULTS: Sixty-three studies were included. To date, most studies showed that the viral mutations, especially the D614G variant, correlate with a higher infectivity than the wild-type virus. However, the evidence of the association between viral mutation and severity of the disease is scant. A SARS-CoV-2 variant with a 382-nucleotide deletion was associated with less severe infection in patients. The 11,083G > U mutation was significantly associated with asymptomatic patients. By contrast, ORF1ab 4715L and S protein 614G variants were significantly more frequent in patients from countries where high fatality rates were also reported. The current evidence showed that variants of concern have led to increased infectivity and deteriorating epidemiological situations. However, the relation between this variant and severity of COVID-19 infection was contradictory. CONCLUSION: The COVID-19 pandemic continues to spread worldwide. It is necessary to anticipate large clinical cohorts to evaluate the virulence and transmissibility of SARS-CoV-2 mutants.

20.
Clin Microbiol Infect ; 27(10): 1516.e1-1516.e6, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1240263

ABSTRACT

OBJECTIVES: To compare the clinical and epidemiological aspects associated with different predominant lineages circulating in Marseille from March 2020 to January 2021. METHODS: In this single-centre retrospective cohort study, characteristics of patients infected with four different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were documented from medical files. The outcome was the occurrence of clinical failure, defined as hospitalization (for outpatients), transfer to the intensive care unit (inpatients) and death (all). RESULTS: A total of 254 patients were infected with clade 20A (20AS), 85 with Marseille-1 (M1V), 190 with Marseille-4 (M4V) and 211 with N501Y (N501YV) variants. 20AS presented a bell-shaped epidemiological curve and nearly disappeared around May 2020. M1V reached a very weak peak, then disappeared after six weeks. M4V appeared in July presented an atypical wave form for 7 months. N501YV has only recently appeared. Compared with 20AS, patients infected with M1V were less likely to report dyspnoea (adjusted odds ratio (OR) 0.50, p 0.04), rhinitis (aOR 0.57, p 0.04) and to be hospitalized (aOR 0.22, p 0.002). Patients infected with M4V were more likely to report fever than those with 20AS and M1V (aOR 2.49, p < 0.0001 and aOR 2.30, p 0.007, respectively) and to be hospitalized than those with M1V (aOR 4.81, p 0.003). Patients infected with N501YV reported lower rate of rhinitis (aOR 0.50, p 0.001) and anosmia (aOR 0.57, p 0.02), compared with those infected with 20AS. A lower rate of hospitalization was associated with N501YV infection compared with 20AS and M4V (aOR 0.33, p < 0.0001 and aOR 0.27, p < 0.0001, respectively). CONCLUSIONS: The four lineages have presentations that differ from one another, epidemiologically and clinically. This supports SARS-CoV-2 genomic surveillance through next-generation sequencing.


Subject(s)
COVID-19/epidemiology , COVID-19/pathology , SARS-CoV-2/pathogenicity , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Child , Child, Preschool , Female , France/epidemiology , Genotype , Hospitalization , Humans , Infant , Infant, Newborn , Intensive Care Units , Male , Middle Aged , Odds Ratio , Retrospective Studies , SARS-CoV-2/classification , SARS-CoV-2/genetics , Severity of Illness Index , Young Adult
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